Background. Tuberculosis remains the leading cause of death due to infectious diseases worldwide ranking above HIV/AIDS, and Nigeria is rated as the 7th worldwide and the 2nd in Africa among the 30 countries highly burdened with tuberculosis worldwide. Aim. To investigate the challenges encountered by nurses in the care of TB patients in a Federal Teaching Hospital in Nigeria. Setting. Ekiti State, Southwest Nigeria. Methods. A qualitative contextual method was utilized with the sample size determined by data saturation. Data collection was done through an audiotaped, semistructured interview. The study sample consisted of 20 professional nurses working in the medical and paediatric wards of a selected Federal Teaching Hospital in South West, Nigeria. Data was analysed using Tesch’s content analysis approach. Results. The majority of the participants were females within the age group of 31–40 years. Challenges included inadequate availability of personal protective equipment (PPE), lack of isolation wards, delegating the care of tuberculosis patients to young inexperienced nurses, long process in diagnosing patients with tuberculosis, lack of policies protecting the nurses from exposure to tuberculosis, and inadequate training. The major concern was the fear of contracting tuberculosis. Conclusion. The study suggested that there should be a provision of adequate personal protective equipment; tuberculosis designated wards and provision of periodic training to update the nurses on care of tuberculosis patients. Establishment and execution of hospital policies and practices along with support are equally essential in facilitating a safe workplace for nurses.